It may also hold opportunities for treating more common forms of dementia, such as Alzheimer’s disease. The new treatment, dubbed CTx1000, targets pathological build-ups of the protein TDP-43 in cells in the brain and spinal cord
Macquarie University neuroscientists have developed a single-dose genetic medicine that has been proven to halt the progression of both motor neurone disease (MND) and frontotemporal dementia (FTD) in mice and may even offer the potential to reverse some of the effects of the fatal diseases.
It may also hold opportunities for treating more common forms of dementia, such as Alzheimer’s disease. The new treatment, dubbed CTx1000, targets pathological build-ups of the protein TDP-43 in cells in the brain and spinal cord.
Cells like neurons produce TDP 43 naturally, and it is important for their healthy function. Under certain conditions, it accumulates in the wrong part of the cells, clogging them and preventing them from working properly. For the past 15 years, a Macquarie University research team led by Professor Lars Ittner has been looking for the causes of this pathological build-up of TDP-43, along with ways to clear the blockages and prevent them from forming in the first place.
The team’s latest findings are published in the prestigious international neuroscience journal, Neuron.
Professor Ittner says their research has furthered their understanding of MND and FTD and their causes.
“We discovered for the first time that where there is pathological TDP-43, there is also an increase in a second protein, 14 3 3,” elaborated Professor Ittner.
“The two proteins interact, resulting in these build-ups in the cells. From this, we were able to isolate a short peptide that controls this interaction, and that’s what we used to create CTx1000. When we administered it in the lab, it dissolved the build-ups, tagging TDP-43 proteins for recycling by the body, and prevented new ones from forming. Importantly, CTx1000 targets only pathological TDP-43, allowing the healthy version of the protein to be produced and go about its work unhindered.”
This makes CTx1000 incredibly safe, and Professor Ittner says they have seen no adverse effects in their studies. “We have great hopes that when this progresses to human trials, it will not only stop people from dying from both MND and FTD, but even allow patients to regain some of the lost function through rehabilitation.”
Professor Yazi Ke, lead author of the new paper, says the milestone is particularly exciting for her because the original discovery was made in her early postdoctoral days. “This spans more than a decade of work, and goes from discovery all the way through to a potential treatment,” she says.
“In lab conditions, we saw CTx1000 stop MND and FTD from progressing even at very advanced stages, and resolving the behavioural symptoms associated with FTD. We have great hopes that when this progresses to human trials, it will not only stop people from dying from both MND and FTD, but even allow patients to regain some of the lost function through rehabilitation.”
Research Fellow Dr Annika van Hummel says they covered a variety of mutations in the TDP genes during lab testing.
“We wanted to prove beyond a doubt that this would work in different situations, and it resulted in clear improvements in both symptoms and brain pathology,” she says.
“The fact that it was effective both before and after the onset of symptoms makes it particularly exciting. While we are initially concentrating on MND and FTD, but about 50 per cent of cases of Alzheimer’s also show TDP pathology, so it’s possible that in the future this treatment could be translatable to other neurodegenerative conditions.”
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